Design of acyclic triaryl olefins: a new class of potent and selective cyclooxygenase-2 (COX-2) inhibitors

Md Jashim Uddin; P N Praveen Rao; Edward E Knaus

doi:10.1016/j.bmcl.2004.01.075

Design of acyclic triaryl olefins: a new class of potent and selective cyclooxygenase-2 (COX-2) inhibitors

Bioorg Med Chem Lett. 2004 Apr 19;14(8):1953-6. doi: 10.1016/j.bmcl.2004.01.075.

Authors

Md Jashim Uddin¹, P N Praveen Rao, Edward E Knaus

Affiliation

¹ Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2N8.

PMID: 15050635
DOI: 10.1016/j.bmcl.2004.01.075

Abstract

A new class of acyclic 1,1-diphenyl-2-(4-methylsulfonylphenyl)-2-alkyl-1-ethenes were synthesized, via a short two-step McMurry olefination reaction and then oxidation of the thiomethyl intermediate using Oxone, in 62-76% yield. The title compounds possess identical C-1 phenyl substituents which precludes the possibility of (Z)- and (E)-stereoisomers. 1,1-Diphenyl-2-(4-methylsulfonylphenyl)hex-1-ene exhibited highly potent (IC(50)=0.014 microM) and selective COX-2 (Selectivity Index >7142) inhibitory activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkenes* / chemical synthesis
Alkenes* / classification
Alkenes* / pharmacology
Animals
Cyclooxygenase 1
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors* / chemical synthesis
Cyclooxygenase Inhibitors* / classification
Cyclooxygenase Inhibitors* / pharmacology
Drug Design*
Isoenzymes / antagonists & inhibitors*
Models, Molecular
Molecular Conformation
Prostaglandin-Endoperoxide Synthases
Stereoisomerism
Structure-Activity Relationship

Substances

Alkenes
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Isoenzymes
Cyclooxygenase 1
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases